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Research key to unlocking pathogenic fungi

12/04/00

Beaverton, OR — A molecular cell biologist at Oregon Graduate Institute of Science and Technology (OGI) is one of four principal investigators in a new two-year, $5.25 million grant from the National Science Foundation (NSF) to sequence the genome of a common fungus that has profound significance for human health and welfare.

The Fungal Genome Initiative may not have the glamour of the Human Genome Project, but its results are nevertheless anxiously awaited in laboratories around the world. That's because understanding the genome of the fungus in question, Neurospora crassa, has implications for agriculture, medicine and environmental science alike, according to Matthew Sachs, an associate professor of biochemistry and molecular biology at OGI.

Like the fruit fly, Neurospora has long served as a powerful laboratory model to study genetics and biological mechanisms, but its genome will be particularly valuable as a guide for interpreting the human genome sequence that's now in hand.

"It's often simplest to look at the function of a gene in fungi and then, once you have a clue concerning its function in the fungi, you can do directed experiments in the higher systems," Sachs said. "It's in many ways a simpler testing ground to assess general aspects of gene function since under the skin the general business of cell biology is the same in Neurospora and higher organisms."

And although Neurospora is not disease-causing itself, it has the ability to provide insights into the entire array of disease-causing fungi, whether they prey on rice, potatoes or humans.

"Researchers are very interested in what makes a fungus pathogenic, and because Neurospora is not pathogenic its genome can serve as a reference," Sachs said. "So when one looks at the genomes of pathogenic fungi one can ask what is different between the pathogen and the nonpathogen, and therefore, we hope, get good clues as to the genes that make organisms medical or agricultural pathogens."

Although agriculturally pathogenic fungi produce billions of dollars of crop losses annually and human-disease-causing fungi are a growing threat to human health worldwide, "We understand very little about the means through which fungal pathogens recognize or colonize hosts, so treatment of infections and defense against these pathogens are largely determined by trial and error today," he added.

Sachs' collaborators include researchers at the Whitehead Institute for Biomedical Research in Cambridge, Mass., the University of Kentucky and the Fungal Genetics Stock Center at the University of Kansas Medical School.

Sachs will be responsible for working with his co-investigators to help clarify the sequencing data for use by the scientific community. They will initiate the annotation of the sequence, they will begin identifying genes and other important features of the genome, and they will develop tools to display the information on the World Wide Web for other researchers and for the lay community.

Deciphering the Neurospora genome will also have implications for environmental science since understanding how the fungi break down dead organisms is critical to better understanding how various ecosystems work.

Researchers have long recognized the scientific usefulness of Neurospora, making it the most intensively investigated member of the filamentous fungi, which are more complex than yeasts and close cousins of mushrooms. But up until now scientists have had to settle with a gradual approach to delving into Neurospora's molecular processes. This project will fundamentally change that.

"The Whitehead Institute can do more sequencing in a day than most individual labs could do in months," Sachs said. "And so there's an urgent need to sequence Neurospora because labs around the world are expending needless effort to obtain sequences instead of doing experiments that are aimed at understanding the biology of the organism."

The initial sequencing data started arriving this month, and Sachs and his colleagues are already at work studying it.

"This is a once-in-a-lifetime opportunity to get at the core of the genome of the organism that I've studied since I started graduate school in 1979," he said, "and I feel fortunate to have that privilege. Plus, as with any scientific project, there's always the strong possibility that the most exciting results are unguessed at present. We don't know exactly what we'll find."